Data in only 18 patients from a project with limited patent life, a partner owed millions down the road and a hugely competitive target market: this being 2021, what’s not to like? Thus shares in Aslan jumped 65% in pre-market trading on hopes for ASLAN004 in atopic dermatitis; the level of efficacy reported certainly makes the project desirable, assuming that it is confirmed in larger trials. Results in a further 16 patients are due mid-2021, with a much larger phase IIb slated for later this year. Efficacy is not the only appeal here: Aslan is striking for once-monthly dosing and hopes that ‘004 will show lower rates of conjunctivitis than Sanofi/Regeneron’s mega-blockbuster Dupixent, which is given every two weeks. The two MAbs are mechanistically very similar, but subtle differences in receptor binding could hold the key to these important differentiations, the company believes. The downsides: ‘004’s inventor CSL is owed considerable milestone payments, and the project’s composition of matter patent expires in 2027. Throw in an incredibly crowded dermatitis space, and is not surprising that Aslan’s roar faded to a 19% share price rise by mid-morning.

Note: selected doses only; *phase IIb trial; **results at wk 12;  ^phase I trial, results at wk 8, per protocol, 7 patients lost to Covid-19 restrictions and other reasons, ITT estimated at 50% and 40% respectively.

Backed by a positive panel meeting Johnson & Johnson’s JNJ-78436735 became the third Covid-19 vaccine granted US emergency use authorisation (EUA), but it is the first that requires only one dose. The company plans to deliver 100 million doses to the US during the first half of the year. An EUA was also granted to Lilly’s bamlanivimab plus etesevimab after the antibody combo significantly cut Covid-19-related hospitalisations and deaths in studies. February saw Bristol Myers Squibb’s Breyanzi become the third anti-CD19 Car-T therapy approved, and the project’s efficacy looks on a par with Gilead’s Yescarta, with less toxicity. However, Breyanzi is even more expensive to manufacture than existing Car-T products. Novartis’s Entresto gained approval in a broad heart failure population, but the group will need to make the most of this before generic competition hits. And Athenex had a knockback for Oraxol, a combination of oral paclitaxel and encequidar, in metastatic breast cancer. The FDA cited toxicity concerns and requested another clinical study. The Pdufa was scheduled for the last day of February and the news, released today, knocked half a billion dollars off the company's market cap.

Interest in adenosine’s role in cancer is growing, and one of the latest in on the act is Teon Therapeutics, a private US biotech that last week closed a $30m series A financing round. The group first floated the possibility of collaborating with Cancer Research UK in December, and today said a deal had been signed: CRUK is to sponsor a phase I/II trial of Teon’s adenosine A2B receptor antagonist TT-702 in cancers including prostate and triple-negative breast. Teon calls TT-702 a “first-in-class” small molecule, though this claim does not stand up to scrutiny. Spain’s Palobiofarma has a pipeline of adenosine antagonists that includes the A2B-specific molecule PBF-1129, which is in two phase I trials in lung and other solid tumours. And Gilead’s 2020 deal with Arcus includes etrumadenant, an inhibitor active at A2A and A2B receptors and already in phase II for NSCLC. Adenosine receptors are overexpressed on some cancers, and a role for the A2B subtype in tumour cell proliferation has recently been proposed. Teon says it will have to pay an undisclosed amount to CRUK in return for rights to the TT-702 data generated.

With its electrical field-emitting Optune device, Novocure has achieved something biotech has repeatedly failed to do: improve the survival of glioblastoma patients. A different version of the device, Optune Lua, is also approved for mesothelioma. Efforts to extend into other cancers, however, have hit a snag, with the company yesterday admitting that several clinical trial readouts would be delayed by Covid-19. Most important of these is Panova-3, the pivotal trial of Optune in pancreatic cancer, whose readout has been pushed back a year. The 14% fall in Novocure’s share price yesterday, though, was also to do with the glioblastoma indication. Medicare coverage for the use of Optune to treat the brain cancer had initially been denied; a reversal of this decision in 2019 has allowed Novocure to appeal previously denied claims, creating a backlog of payments and swelling the group’s top and bottom lines. This backlog has now been pretty much exhausted, so many analysts expect Novocure’s sales to grow much more slowly in the coming years. R&D expenses are also taking their toll, with the company sponsoring an astonishing 34 active clinical trials, 26 of which are in brain tumours. 

With Sarepta already running a confirmatory trial of its third exon-skipping Duchenne muscular dystrophy therapy, its US accelerated approval last night perhaps lacked the drama of earlier green lights. Moreover, though the label of the drug now branded Amondys 45 is backed by a surrogate endpoint, dystrophin expression, there is a placebo comparator. In this regard Sarepta is gaining credibility: its first two DMD exon skippers, Exondys 51 and Vyondys 53, got accelerated approvals based on small, uncontrolled studies. The former’s confirmatory trial did not even start for another four years, and the latter had to contend with a complete response letter. The Essence study will seek to confirm the approvals of Vyondys and Amondys alike, and Amondys’s conditional green light is backed by early data from this same trial. If Sarepta dragged its feet it was not alone: US data show that, of 23 accelerated approvals granted in 2010-20 to non-oncology drugs, only four had converted to full approvals through clinical confirmation as at the end of 2020, taking an average of 3.5 years to do so. And as-yet unconverted accelerated approvals for Makena, Ferriprox and Sirturo date back to 2011-12.

Bluebird’s exclusive disclosure yesterday regarding two crucially important cancer cases that this month caused Lentiglobin clinical trials to be halted sent its stock up 8%. This is great news, therefore – unless you happen not to have registered for the investor conference where the bombshell was dropped. The revelations concerned further analysis of Lentiglobin’s phase I/II sickle cell disease trial, where one subject had developed acute myeloid leukaemia and another myelodysplastic syndrome. They were made at yesterday’s SVB Leerink healthcare conference rather than in a regulatory filing, flying in the face of the company’s promise 10 days ago to be transparent. The gist is that both patients had had very severe sickle cell disease, that the AML might have occurred independently of the vector that delivers Lentiglobin, and that the MDS might not have been MDS at all. Bluebird is continuing its investigation, and the complete analysis of the AML case could now come in a couple of weeks. Yesterday the company’s chief executive, Nick Leschly, said: “We are going to be as transparent as we can be with all stakeholders.” All investors really deserve better.

The number of US approvals via the accelerated pathway has soared in recent years, particularly in oncology, recent Evaluate Vantage analyses have shown. And there are hints that conversions to full approval are accelerating, as suggested by the chart below. Still, two thirds of the 130 drugs approved on an accelerated basis in the last decade have yet to be converted, and more energy could be expended by the agency and sponsors alike. The data reveal some of the worst offenders, with Amag’s Makena, now owned by Covis, an extreme example. The FDA has proposed withdrawing the controversial preterm birth treatment, but foot-dragging by its owners means that it is still available. It is also notable that Tykerb and Istodax were both commercial flops, while the likes of Imbruvica and Alimta went on to become huge blockbusters. This is not to say that time to convert is always correlated with success; Imbruvica has three accelerated approvals outstanding, the first won seven and a half years ago.

Last week Evaluate Vantage looked at the biggest one-day share price moves caused by Covid-19-related activities. An examination of the biggest one-day gainers in terms of market cap, using EvaluatePharma’s EventAnalyzer, reveals a similarly startling picture. Some of these gigantic moves occurred for sensible reasons: it is hard to argue with the importance of the superb pivotal trial data on Moderna’s Covid-19 vaccine, for instance. Others, such as Gilead’s decision to start trials of remdesivir resulting in a $5.8bn valuation bump, and Regeneron adding $4.2bn simply because its antibody doublet was used to treat a hospitalised Donald Trump, are rather more preposterous. It is notable that the market cap of these last two companies subsequently dropped by $14bn apiece. It should also be mentioned that two of the movers in the table below, Abcellera and Curevac, recorded much bigger one-day market cap rises – of $10.3bn and $6.6bn respectively – on their first days as public companies. While these gains cannot be specifically attributed to Covid-19, enthusiasm for companies active in this space will certainly have played a part. 

Brainstorm Cell Therapeutics is today facing a monumental decision: quit all developmental work on its lead asset in its most advanced indication or press on with a regulatory filing despite a dire warning from the US FDA on the project's chances of success. However, this might feel like déjà vu for investors. Back in November Brainstorm decided to try to file its autologous cell therapy treatment NurOwn in ALS despite the unequivocal failure of its pivotal trial. Today the agency made its position clear, stating that the clinical data Brainstorm has submitted did not meet its threshold for filing. However, in what must be an acknowledgement of what a terrible disease ALS is, the agency did not preclude Brainstorm from proceeding with a BLA submission. But, even with the support of patient groups desperate for a cure, it is hard to see how Brainstorm will succeed without further clinical trials and, with only $42m in the bank, funding those trials and its other work in multiple sclerosis might be a struggle. However, while Brainstorm’s next move might be slightly opaque, investors were very clear where they stood, with shares falling by 30% in early trading today.

Shares in Immunome jumped 76% yesterday after the company claimed to have isolated “potent antibodies” capable of neutralising several worrying SARS-CoV-2 variants, the result of very early discovery work that in today’s market is apparently worth $177m. This is far from the most egregious valuation surge triggered by Covid-19 claims, however, examples of which can be found from the very start of the pandemic. EvaluatePharma’s EventAnalyzer helps pinpoint some of the biggest percentage one-day gains seen over the past 12 months. Almost all of these groups used the opportunity to raise money, and most have failed to deliver on hopes. Ocugen stands out as a big beneficiary, for now at least. The company was a penny stock a mere 10 weeks ago, and executives were poised to ask shareholders to agree to a painful reverse split to prevent the stock’s banishment from Nasdaq. A deal with the Indian vaccines group Bharat Biotech changed its fortunes, and the initial near tripling of Ocugen’s shares was only the beginning of the gains. This is an exception rather than the rule, of course, something that those chasing Immunome yesterday would do well to remember.